tbuckley/cabot-search huggingface dataset:
A pH/H<sub>2</sub>O<sub>2</sub>/MMP9 Time‐Response Gel System with Sparc<sup>high</sup> Tregs Derived Extracellular Vesicles Promote Recovery After Acute Myocardial Infarction
Authors: Panke Cheng, Lianying Cheng, Hukui Han, Junlin Li, Cui Ma, Hui Huang, Jie Zhou, Jiayue Feng, Yu Huang, Yipin Lv, Huihui Huang, Yiren Wang, Lingmi Hou, Yang Chen, Gang Li
Journal: Advanced Healthcare Materials (2022)

Regulatory T cells overexpressing SPARC (secreted protein acidic and cysteine rich) (Sparchigh Tregs) can help repair infarct tissues after acute myocardial infarction (AMI). This research demonstrates that Sparchigh Treg-derived extracellular vesicles (EVs) effectively improved cardiac function through proinflammatory factors IL-1β, IL-6, and TNF-α inhibition and collagen synthesis related gene Col3a1 promotion in AMI; moreover, a composite hydrogel-EVs system (DHPM(4APPC)_EVs) is designed based on Sparchigh Treg-derived EVs with CXCR2 overexpressing and pH/H2 O2 /MMP9 temporally responsive gel microspheres. In AMI, due to the levels of chemokine, pH, H2 O2 , and MMP9 enzymes in the infarct area, DHPM(4APPC)_EVs can effectively target the infarct area, release the loaded EVs, form the gel to capture the released EVs, and slowly release the captured EVs, contribute to promote EVs to stay in the infarct area for a long time to play the repair function, so as to reduce myocardial injury and promote the improvement of cardiac function. The proposed system in this research provides a potential approach for the treatment of AMI in the future.
Adverse Drug Events in Hospitalized Patients&lt;subtitle&gt;Excess Length of Stay, Extra Costs, and Attributable Mortality&lt;/subtitle&gt;
Authors: David C. Classen
Journal: JAMA (1997)

<h3>Objective.</h3> —To determine the excess length of stay, extra costs, and mortality attributable to adverse drug events (ADEs) in hospitalized patients. <h3>Design.</h3> —Matched case-control study. <h3>Setting.</h3> —The LDS Hospital, a tertiary care health care institution. <h3>Patients.</h3> —All patients admitted to LDS Hospital from January 1, 1990, to December 31,1993, were eligible. Cases were defined as patients with ADEs that occurred during hospitalization; controls were selected according to matching variables in a stepwise fashion. <h3>Methods.</h3> —Controls were matched to cases on primary discharge diagnosis related group (DRG), age, sex, acuity, and year of admission; varying numbers of controls were matched to each case. Matching was successful for 71% of the cases, leading to 1580 cases and 20197 controls. <h3>Main Outcome Measures.</h3> —Crude and attributable mortality, crude and attributable length of stay, and cost of hospitalization. <h3>Results.</h3> —ADEs complicated 2.43 per 100 admissions to the LDS Hospital during the study period. The crude mortality rates for the cases and matched controls were 3.5% and 1.05%, respectively (<i>P</i>&lt;.001). The mean length of hospital stay significantly differed between the cases and matched controls (7.69 vs 4.46 days;<i>P</i>&lt;.001) as did the mean cost of hospitalization ($10010 vs $5355;<i>P</i>&lt;.001). The extra length of hospital stay attributable to an ADE was 1.74 days (<i>P</i>&lt;.001). The excess cost of hospitalization attributable to an ADE was $2013 (<i>P</i>&lt;.001). A linear regression analysis for length of stay and cost controlling for all matching variables revealed that the occurrence of an ADE was associated with increased length of stay of 1.91 days and an increased cost of $2262 (<i>P</i>&lt;.001). In a similar logistic regression analysis for mortality, the increased risk of death among patients experiencing an ADE was 1.88 (95% confidence interval, 1.54-2.22;<i>P</i>&lt;.001). <h3>Conclusion.</h3> —The attributable lengths of stay and costs of hospitalization for ADEs are substantial. An ADE is associated with a significantly prolonged length of stay, increased economic burden, and an almost 2-fold increased risk of death.
Revised <scp>MALT‐IPI</scp>: A new predictive model that identifies high‐risk patients with extranodal marginal zone lymphoma
Authors: Juan Pablo Alderuccio, Isildinha M. Reis, Thomas M. Habermann, Brian K. Link, Catherine Thieblemont, Annarita Conconi, Melissa C. Larson, Luciano Cascione, Wei Zhao, James R. Cerhan, Emanuele Zucca, Izidore S. Lossos
Journal: American Journal of Hematology (2022)

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous disease with a subset of patients exhibiting a more aggressive course. We previously reported that EMZL with multiple mucosal sites (MMS) at diagnosis is characterized by shorter survival. To better recognize patients with different patterns of progression-free survival (PFS) we developed and validated a new prognostic index primarily based on patient's disease characteristics. We derived the "Revised mucosa-associated lymphoid tissue International Prognostic Index" (Revised MALT-IPI) in a large data set (n = 397) by identifying candidate variables that showed highest prognostic association with PFS. The revised MALT-IPI was validated in two independent cohorts, from the University of Iowa/Mayo Clinic (n = 297) and from IELSG-19 study (n = 400). A stepwise Cox regression analysis yielded a model including four independent predictors of shorter PFS. Revised MALT-IPI has scores ranging from 0 to 5, calculated as a sum of one point for each of the following- age >60 years, elevated LDH, and stage III-IV; and two points for MMS. In the training cohort, the Revised MALT-IPI defined four risk groups: low risk (score 0, reference group), low-medium risk (score 1, HR = 1.85, p = .008), medium-high risk (score 2, HR = 3.84, p < .0001), and high risk (score 3+, HR = 8.48, p < .0001). Performance of the Revised MALT-IPI was similar in external validation cohorts. Revised MALT-IPI is a new index centered on disease characteristics that provides robust risk-stratification identifying a group of patients characterized by earlier progression of disease. Revised MALT-IPI can allow a more disease-adjusted management of patients with EMZL in clinical trials and practice.
Comparison of Colonoscopy, Fecal Immunochemical Test, and Risk-Adapted Approach in a Colorectal Cancer Screening Trial (TARGET-C)
Authors: Hongda Chen, Jufang Shi, Ming Lu, Yanjie Li, Lingbin Du, Xianzhen Liao, Donghua Wei, Dong Dong, Yi Gao, Chen Zhu, Rongbiao Ying, Weifang Zheng, Shipeng Yan, Haifan Xiao, Juan Zhang, Yunxin Kong, Furong Li, Shuangmei Zou, Chengcheng Liu, Hong Wang, Yuhan Zhang, Bin Lu, Chenyu Luo, Jie Cai, Jianbo Tian, Xiaoping Miao, Kefeng Ding, Hermann Brenner, Min Dai
Journal: Clinical Gastroenterology and Hepatology (2022)

The screening yield and related cost of a risk-adapted screening approach compared with established screening strategies in population-based colorectal cancer (CRC) screening are not clear.
Mechanistic Target of Rapamycin Inhibition Prevents Coronary Artery Remodeling in a Murine Model of Kawasaki Disease
Authors: Angus T. Stock, Sarah Parsons, Damian B. D'Silva, Jacinta A. Hansen, Varun J. Sharma, Fiona James, Graham Starkey, Rohit D'Costa, Claire L. Gordon, Ian P. Wicks
Journal: Arthritis & Rheumatology (2022)

Remodeling of the coronary arteries is a common feature in severe cases of Kawasaki disease (KD). This pathology is driven by the dysregulated proliferation of vascular fibroblasts, which can lead to coronary artery aneurysms, stenosis, and myocardial ischemia. We undertook this study to investigate whether inhibiting fibroblast proliferation might be an effective therapeutic strategy to prevent coronary artery remodeling in KD.We used a murine model of KD (induced by the injection of the Candida albicans water-soluble complex [CAWS]) and analyzed patient samples to evaluate potential antifibrotic therapies for KD.We identified the mechanistic target of rapamycin (mTOR) pathway as a potential therapeutic target in KD. The mTOR inhibitor rapamycin potently inhibited cardiac fibroblast proliferation in vitro, and vascular fibroblasts up-regulated mTOR kinase signaling in vivo in the CAWS mouse model of KD. We evaluated the in vivo efficacy of mTOR inhibition and found that the therapeutic administration of rapamycin reduced vascular fibrosis and intimal hyperplasia of the coronary arteries in CAWS-injected mice. Furthermore, the analysis of cardiac tissue from KD fatalities revealed that vascular fibroblasts localizing with inflamed coronary arteries up-regulate mTOR signaling, confirming that the mTOR pathway is active in human KD.Our findings demonstrate that mTOR signaling contributes to coronary artery remodeling in KD, and that targeting this pathway offers a potential therapeutic strategy to prevent or restrict this pathology in high-risk KD patients.
A Biodegradable Metal‐Polymer Composite Stent Safe and Effective on Physiological and Serum‐Containing Biomimetic Conditions
Authors: Hongjie Zhang, Wanqian Zhang, Hong Qiu, Gui Zhang, Xin Li, Haiping Qi, Jingzhen Guo, Jie Qian, Xiaoli Shi, Xian Gao, Daokun Shi, Deyuan Zhang, Runlin Gao, Jiandong Ding
Journal: Advanced Healthcare Materials (2022)

The new-generation coronary stents are expected to be biodegradable, and then the biocompatibility along with biodegradation becomes more challenging. It is a critical issue to choose appropriate biomimetic conditions to evaluate biocompatibility. Compared with other candidates for biodegradable stents, iron-based materials are of high mechanical strength, yet have raised more concerns about biodegradability and biocompatibility. Herein, a metal-polymer composite strategy is applied to accelerate the degradation of iron-based stents in vitro and in a porcine model. Furthermore, it is found that serum, the main environment of vascular stents, ensured the safety of iron corrosion through its antioxidants. This work highlights the importance of serum, particularly albumin, for an in vitro condition mimicking blood-related physiological condition, when reactive oxygen species, inflammatory response, and neointimal hyperplasia are concerned. The resultant metal-polymer composite stent is implanted into a patient in clinical research via interventional treatment, and the follow-up confirms its safety, efficacy, and appropriate biodegradability.
The Tympanic Membrane
Authors: Allan P. Wolff
Journal: JAMA (1973)

A cough can be caused by a hair lying against the tympanic membrane. To the best of our knowledge, this is documented for the first time by our report of three patients with chronic cough who experienced relief after a hair was removed from the ear drum. The explanation for this observation is based on a protective reflex mediated through afferent vagal nerve fibers.
Three-dimensional micro-structurally informed in silico myocardium—Towards virtual imaging trials in cardiac diffusion weighted MRI
Authors: Mojtaba Lashgari, Nishant Ravikumar, Irvin Teh, Jing-Rebecca Li, David L. Buckley, Jurgen E. Schneider, Alejandro F. Frangi
Journal: Medical Image Analysis (2022)

In silico tissue models (viz. numerical phantoms) provide a mechanism for evaluating quantitative models of magnetic resonance imaging. This includes the validation and sensitivity analysis of imaging biomarkers and tissue microstructure parameters. This study proposes a novel method to generate a realistic numerical phantom of myocardial microstructure. The proposed method extends previous studies by accounting for the variability of the cardiomyocyte shape, water exchange between the cardiomyocytes (intercalated discs), disorder class of myocardial microstructure, and four sheetlet orientations. In the first stage of the method, cardiomyocytes and sheetlets are generated by considering the shape variability and intercalated discs in cardiomyocyte—cardiomyocyte connections. Sheetlets are then aggregated and oriented in the directions of interest. The morphometric study demonstrates no significant difference (p>0.01) between the distribution of volume, length, and primary and secondary axes of the numerical and real (literature) cardiomyocyte data. Moreover, structural correlation analysis validates that the in-silico tissue is in the same class of disorderliness as the real tissue. Additionally, the absolute angle differences between the simulated helical angle (HA) and input HA (reference value) of the cardiomyocytes (4.3°±3.1°) demonstrate a good agreement with the absolute angle difference between the measured HA using experimental cardiac diffusion tensor imaging (cDTI) and histology (reference value) reported by (Holmes et al., 2000) (3.7°±6.4°) and (Scollan et al. 1998) (4.9°±14.6°). Furthermore, the angular distance between eigenvectors and sheetlet angles of the input and simulated cDTI is much smaller than those between measured angles using structural tensor imaging (as a gold standard) and experimental cDTI. Combined with the qualitative results, these results confirm that the proposed method can generate richer numerical phantoms for the myocardium than previous studies.
Advisory Board and Contents
Authors: Eliana Hadjiandreou, Daryl Cameron, Á Miklósi, Friederike Range, Sarah Marshall-Pescini, Alain Van Hiel, Mark Brandt, Bert Bakker, Jacob Miller, Kevin Weiner Editor, Lindsey Drayton, Danielle Loughlin, Rolf Van Der Sanden, Patrick Scheffmann, Ralph Adolphs, Renee Baillargeon, Nick Chater, Peter Dayan, Stanislas Dehaene, Daniel Dennett, Yadin Dudai, Andreas Engel, Martha Farah, Angela Friederici, Okihide Hikosaka, Ray Jackendoff, Philip Johnson-Laird, Nancy Kanwisher, Christof Koch, Marta Kutas, Nikos Logothetis, James Mcclelland, Earl Miller, Elizabeth Phelps, Russell Poldrack, Marcus Raichle, Trevor Robbins, Anthony Wagner, Vincent Walsh
Journal: Trends in Cognitive Sciences (2022)
Pseudomonas aeruginosa bloodstream infection in patients with hematological diseases: Clinical outcomes and prediction model of multidrug-resistant infections
Authors: Yuanqi Zhao, Qingsong Lin, Tingting Zhang, Sisi Zhen, Jieru Wang, Erlie Jiang, Yingchang Mi, Lugui Qiu, Mingzhe Han, Jianxiang Wang, Sizhou Feng
Journal: Journal of Infection (2022)
The Pathogenesis of African Trypanosomiasis
Authors: Etienne Pays, Magdalena Radwanska, Stefan Magez
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

African trypanosomes are bloodstream protozoan parasites that infect mammals including humans, where they cause sleeping sickness. Long-lasting infection is required to favor parasite transmission between hosts. Therefore, trypanosomes have developed strategies to continuously escape innate and adaptive responses of the immune system, while also preventing premature death of the host. The pathology linked to infection mainly results from inflammation and includes anemia and brain dysfunction in addition to loss of specificity and memory of the antibody response. The serum of humans contains an efficient trypanolytic factor, the membrane pore-forming protein apolipoprotein L1 (APOL1). In the two human-infective trypanosomes, specific parasite resistance factors inhibit APOL1 activity. In turn, many African individuals express APOL1 variants that counteract these resistance factors, enabling them to avoid sleeping sickness. However, these variants are associated with chronic kidney disease, particularly in the context of virus-induced inflammation such as coronavirus disease 2019. Vaccination perspectives are discussed.
Reply
Authors: Yi‐Te Lee, Yazhen Zhu, Ju Dong Yang, Vatche G. Agopian, Hsian‐Rong Tseng
Journal: Hepatology (2022)

We appreciate the interest of Luo et al. in our study1 demonstrating an extracellular vesicle (EV)‐based protein assay for detecting early‐stage hepatocellular carcinoma (HCC). We would like to respond to the concerns raised by the authors. The current clinical practice guideline suggests routine surveillance only for the patients at risk for developing HCC2 rather than the general healthy populations. It is very critical to limit the study populations only to the patients who are at risk to avoid overestimation of the performance of an early detection biomarker.3 The appropriate study design for evaluating an early detection biomarker for HCC has been elaborated in a recent White Paper provided by experts on HCC biomarker development.3 As delineated in our introduction, our study's aim was to develop early detection biomarkers for HCC that can be tested among populations who are at risk, and not the general population. Therefore, assessing the specificity of the biomarker for HCC over other malignancies was not a priority in the current study. Nonetheless, the HCC EV ECG score (calculated from the readouts of EpCAM+ CD63+, CD147+ CD63+, and GPC3+ CD63+ EVs) was in fact highest in patients with HCC compared with patients with other cancers, emphasizing its specificity for HCC (Figure S14). This is a phase 2 biomarker study to assess potential EV‐based protein markers in detecting HCC and we have provided the justification for marker selection. In response to the consideration of SMAD Family Member 3 (SMAD3), we would like to point out that SMAD3 exhibited relatively limited performance in distinguishing HCC from healthy donors (area under the receiver operating characteristic curve, 0.70) according to the results of the previous study.4,5 Additionally, the study did not restrict the HCC to early‐stage cases, which would overestimate its performance.3,4 Finally, we agree that the cost‐effectiveness of any biomarker should be fully evaluated before its clinical implementation. Although it was beyond the scope of our current study, cost‐effectiveness of HCC EV ECG score will be further investigated in the future, in parallel with a larger scale external validation.
Efficacy of Midodrine vs Placebo in Neurogenic Orthostatic Hypotension
Authors: Phillip A. Low
Journal: JAMA (1997)

<h3>Objective.</h3> —To evaluate the efficacy of a 10-mg dose of midodrine 3 times per day in improving blood pressure (BP) and ameliorating symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension. Midodrine hydrochloride, an α=agonist, could improve orthostatic BP by increasing vasomotor and venomotor tone. <h3>Design/Methods.</h3> —A total of 171 patients with orthostatic hypotension participated in a multicenter, randomized, placebo-controlled study. They were randomized to a 10-mg dose of midodrine or placebo 3 times per day in a 6-week study, comprising single-blind run-in (at week 1) and washout at weeks 5 and 6, with an intervening double-blind period (weeks 2 to 4). <h3>Setting.</h3> —Twenty-five centers, with most patients evaluated in referral centers. <h3>Main Outcome Measures.</h3> —The primary end points were improvement in standing systolic BP, symptoms of lightheadedness, and a global symptom relief score (by the investigator and patient separately). <h3>Results.</h3> —Nine patients were not evaluable because of noncompliance or taking concomitant vasoactive medications (3 in the midodrine group, 6 in the placebo group). In the evaluable patients, midodrine resulted in improvements in standing systolic BP at all time points (<i>P</i>&lt;.001 at visits 2,3,4, and 5), in reported symptoms by the end of the second week of treatment (<i>P</i>=.001), and in the global symptom relief score rated by both the patient (<i>P</i>=.03) and the investigator (<i>P</i>&lt;.001). There was no effect by center, severity of orthostatic hypotension, use of fludrocortisone or compression garments, or diagnosis. The main adverse effects were those of pilomotor reactions, urinary retention, and supine hypertension. <h3>Conclusions.</h3> —Midodrine is efficacious and safe in the treatment of neurogenic orthostatic hypotension.
Repression of the antiporter SLC7A11/glutathione/glutathione peroxidase 4 axis drives ferroptosis of vascular smooth muscle cells to facilitate vascular calcification
Authors: Yuanzhi Ye, An Chen, Li Li, Qingchun Liang, Siyi Wang, Qianqian Dong, Mingwei Fu, Zirong Lan, Yining Li, Xiaoyu Liu, Jing-Song Ou, Lihe Lu, Jianyun Yan
Journal: Kidney International (2022)
Post-vaccination SARS-CoV-2 antibody kinetics and protection duration against Omicron in elderly population
Authors: Chloé Dimeglio, Pauline Trémeaux, Fabrice Herin, Isabelle Da-Silva, Marion Porcheron, Guillaume Martin-Blondel, Caroline Gernigon, Sabine Chapuy-Regaud, Hélène Villars, Jacques Izopet
Journal: Journal of Infection (2022)
Factor H related proteins modulate complement activation on kidney cells
Authors: Brandon Renner, Jennifer Laskowski, Felix Poppelaars, Viviana P. Ferreira, Judith Blaine, Alexandra H. Antonioli, Jonathan P. Hannan, James M. Kovacs, Cees van Kooten, Zhiying You, Matthew C. Pickering, V. Michael Holers, Joshua M. Thurman
Journal: Kidney International (2022)
Dynamics of immune responses to inactivated COVID-19 vaccination over 8 months in China
Authors: Tianpei Shi, Mu-Xian Dai, Feng-Wei Liu, Jun Hu, Mu-Hua Feng, Gang-Xu Xu, Ya-Jing Wang, Li-Hong Zhang, Liang Zhang, Zijie Zhang, Tai-Cheng Zhou, Jia Wei
Journal: Journal of Infection (2022)
Decline in US Childhood Cancer Mortality
Authors: Robert W. Miller
Journal: JAMA (1984)

Cancer mortality among children in the United States, 1950 through 1979, as evaluated by death certificate diagnoses, revealed dramatic declines primarily in the second half of the 30-year interval. The numbers of deaths of persons younger than 15 years, 1965 through 1979, as compared with the number expected at 1950 rates, fell 50% for leukemia, 32% for non-Hodgkin's lymphoma, 80% for Hodgkin's disease, 50% for bone sarcoma, 68% for kidney cancer, and 31% for all other cancer. There were 17,411 fewer deaths from childhood cancer from 1965 through 1979 than expected at the 1950 rate. Leukemia mortality declined by 8,073 deaths and kidney tumor mortality by 2,393. In data subsequently received for 1980, the decline in rates persisted for leukemia and non-Hodgkin's lymphoma, but the rates for the other four cancer categories seem to have reached a plateau. The reduction in mortality is attributed to improved therapy. (<i>JAMA</i>1984;251:1567-1570)
Effects of Formaldehyde on the Mucous Membranes and Lungs
Authors: Edward P. Horvath
Journal: JAMA (1988)

One hundred nine workers and 254 control subjects were studied to evaluate the effects of formaldehyde on the mucous membranes and lungs. A modified, respiratory symptom questionnaire and spirometry were administered to all study participants before and after their work shift, and formaldehyde levels were determined for each test subject. Over the course of the monitored work shift, test subjects demonstrated a dose-dependent excess of irritant symptoms and a statistically significant decline in certain lung function parameters. Analysis of test and control subject data combined revealed a correlation between formaldehyde exposure and these pulmonary changes. Baseline spirometry values were not significantly different between test and control groups, and formaldehyde-exposed workers did not report an excess of respiratory symptoms. Formaldehyde is a dose-dependent irritant of the eyes and mucous membranes at low-level exposures. It can exert a small, across-shift effect on airways but after a mean exposure of ten years does not appear to cause permanent respiratory impairment. (<i>JAMA</i>1988;259:701-707)
Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function
Authors: MeiLan K. Han, Wen Ye, Di Wang, Emily White, Mehrdad Arjomandi, Igor Z. Barjaktarevic, Stacey-Ann Brown, Russell G. Buhr, Alejandro P. Comellas, Christopher B. Cooper, Gerard J. Criner, Mark T. Dransfield, Frank Drescher, Rodney J. Folz, Nadia N. Hansel, Ravi Kalhan, Robert J. Kaner, Richard E. Kanner, Jerry A. Krishnan, Stephen C. Lazarus, Veeranna Maddipati, Fernando J. Martinez, Anne Mathews, Catherine Meldrum, Charlene McEvoy, Toru Nyunoya, Linda Rogers, William W. Stringer, Christine H. Wendt, Robert A. Wise, Stephen R. Wisniewski, Frank C. Sciurba, Prescott G. Woodruff
Journal: New England Journal of Medicine (2022)

Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking.